Stay tuned for details on our 4th annual Huddle Up for Autism, when CAR and the Philadelphia Eagles join together once again to bring families living with autism a day of fun, education, and awareness at Lincoln Financial Field.
I am a molecular geneticist. I joined the Department of Psychiatry at the the University of Pennsylvania in 1990 and the Department of Genetics in 2002. Research in my laboratory involves identification of the genetic basis of behavioral and psychiatric disorders. To complement ongoing efforts in human psychiatric genetics, my laboratory has embarked over the last several years on two main projects: a screen for novel behavioral mutations in the mouse and the functional annotation of the mammalian genome using bioinformatics approaches. Our goal is to identify candidate sequences for neuropsychiatric and developmental disorders.
Our work on the Rab3A mutants in the mouse led us to disorders of the synapse in humans. Based on our findings, we expect that mutations in a large number of synaptic genes will lead to a wide range of behavioral and neurodevelopmental anomalies. My laboratory, in collaboration with computational biologists at the University of Pennsylvania, is involved in the identification and characterization of highly conserved sequence motifs in and around synaptic genes using computational and experimental approaches. This effort is particularly important in light of reports on several promising genetic variants associated with autism, which do not cause changes in amino-acid sequence, but map to non-coding regions.
Recent genetic and neuroimaging studies have shown that the cause of autism may be linked to abnormalities in the synapse. In collaboration with the Center for Applied Genomics at the Children’s Hospital of Philadelphia, my lab is involved in the genetic analysis of child-parent trios from the Autism Genetics Resource Exchange (AGRE) collection. Our data support previous reports showing that there is wide-spread copy number variation (CNV) in the human genome, including small duplications and deletions, which are either inherited or arise de novo. We are developing and using a wide range of novel bioinformatics tools to identify autism susceptibility loci and assess their role in other disorders.
In my view, the higher rate of deleterious mutations in our genome than originally expected and the need to assess the phenotypic consequences of these variants represent new challenges in autism research and in studies of other neurodevelopmental and psychiatric disorders.
In addition to the work in my laboratory and in the Center for Autism Research, I am involved in autism research through a collaboration with AGRE (Autism Speaks) and a collaboration with Dubravka Hranilovic, Ph.D. on studies of autism in Croatia.
Sample of Significant Publications
Hadley D, Murphy T, Ungar L, Kim J, Bucan M. Patterns of Sequence Conservation in Presynaptic Neural Genes. Genome Biology. 2006. I7(11): R105.
The Autism Genome Project Consortium. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet. Mar 2007. 39(3): 319-28.
Wang K, Li M, Bucan M. Pathway-based approaches for analysis of genome-wide association studies. Am. J. of Human Genetics. 2007. 81: 6.
Wang K, Li M, Hadley D, Liu R, Glessner J, Grant S, Hakonarson H, Bucan M. High-resolution copy number variation detection: application of an integrated hidden Markov Model on whole-genome SNP genotyping data. Genome Research. 2007. 17: 1665-1674.
Yang S, Van Dongen H, Wang K, Berrettini W, Bucan M. Assessment of circadian function in fibroblasts derived from bipolar patients. Molecular Psychiatry. 2007. [Epub ahead of print].